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Title: Characterisation of ovine and human vertebral endplates using X-ray microtomography : the effects of degeneration on structure
Author: Gurrib, Sheen
ISNI:       0000 0004 9359 9218
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2020
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Back pain is a significant and debilitating problem worldwide. It can be caused by several factors, but the cause of pain is only identified successfully in a minority of cases. There has been significant evidence indicating that the vertebral endplate (VEP) plays a major role in low back pain. The VEP balances two conflicting biophysical functions: providing both a nutritional pathway and mechanical support to the disc, therefore making it prone to damage. However, the VEP is still poorly characterised. This thesis describes work undertaken to characterise the structure of normal and degenerative VEPs. Initially, ovine VEPs were used to investigate the effect of location along the spine on the structural properties of the VEP. Next, the network of canals within the VEP was characterised in terms of canal architecture, content and endings at the disc boundary. Finally, the effect of degeneration on the structural properties was investigated in human endplates. Sheep spines were used as a model for the human spine to develop experimental protocols, due to similarities in their morphological and biomechanical features. A protocol was developed, using micro-computed tomography (micro-CT), for the structural characterisation of sheep VEPs. This is the first time that simultaneous assessment of different structural properties of the same VEP has been reported, allowing the comparison of structural features at different VEP locations on the same spine. The central region of the VEP was thinner than the periphery at all spinal levels and this could be explained by the increased biochemical exchange with the central nucleus pulposus of the disc and by the requirement of strong anchorage of disc fibres for mechanical support in the peripheral regions. Cranial VEPs were thicker, more porous and showed higher bone mineral density than their caudal counterparts. VEPs at different spinal levels also exhibited different structural properties. The thickest VEP measured was 1.010 ± 0.014 mm at the anterior region at cranial side of L5/L6 and the thinnest VEP was 0.455 ± 0.025 mm at the central region at caudal side of L3/L4. A series of intricate 3D canal networks within the ovine VEP layer was analysed. These networks were found to connect the marrow spaces in the vertebra to the soft tissues of the disc. Evidence of the presence of blood within these canals was shown using photoacoustic imaging, and the ending of the vessels were identified as bud-like protrusions, emerging out of the VEP layer. The individual canals were characterised in terms of their length, cross-sectional diameter and orientation. A high density of canals perpendicular to the VEP surface and emerging out of the VEP boundary was seen in the central region, of up to 39 ± 8 canal openings/mm2 for the caudal VEP at the spinal level L3/L4, providing further evidence for the increased nutritional exchange with the nucleus pulposus. This study is the first to characterise the structure of the individual canals, and simultaneously investigate the contents and the endings of these canals. A novel approach was also developed for the comparison of the clinical assessments of disc degeneration, from magnetic resonance imaging (MRI) scans, to laboratory characterisation of the human VEP from micro-CT imaging, using samples from patients undergoing elective surgery. The results suggest that the hindered nutritional pathway within the VEP was more likely to be an initiating factor of disc degeneration, rather than the effect. The structural properties of the VEP were seen to change with levels of disc degeneration, assessed by Modic types, Pfirrmann grades and VEP erosion grades. The bone mineral density showed an increasing trend from Modic type I (0.108 ± 0.007 gcm-3) to type III (0.139 ± 0.004 gcm-3). The Pfirrmann grading system was found to be limited in its assessment of progressive degeneration, while advancing VEP erosion grades was correlated with increasing sizes of the canal openings on the VEP surface. The findings also showed that the sheep model, although useful for optimising testing protocols, was not a realistic representation of the human spine. This body of work shows the importance of the VEP in maintaining the healthy functioning of the disc, given its key role in providing nutrition and mechanical support to the disc. Evidence is also provided to correlate spinal degeneration with structural changes in the VEP. Equipped with knowledge of the structure and functions of the VEP, it will be possible to identify the areas prone to damage and therefore the aetiology of degeneration can be clarified.
Supervisor: Cameron, Ruth ; Best, Serena Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: vertebral endplates ; spine ; micro computed tomography ; backpain